The proliferation of estrogen (E)-sensitive human breast tumor cells (MCF7, T47D) in an "in animal-in culture" system is the central issue studied in this lab. The effect of estradiol-17 beta (E[unreadable]2[unreadable]) on specific protein synthesis and its relation with the proliferation of these E[unreadable]2[unreadable] target cells is being characterized. These cells carry estrophilins and multiply faster in nude mice to which E[unreadable]2[unreadable] is administered than in those in which E[unreadable]2[unreadable] is lacking. In culture conditions, charcoal-dextran stripped human sera inhibit the proliferation of these cells in dose-dependent pattern; estrogens cancel this inhibition. These and additional data are compatible with the notion of an indirect and negative control of the proliferation of E[unreadable]2[unreadable]-sensitive cells. The specific aims of this grant are to purify the specific inhibitors of the proliferation of E[unreadable]2[unreadable]-sensitive human cells (estrocolyones) and determine the effect of triphenylethylenes ("antiestrogens") on the proliferation of the above mentioned cells within the context of the indirect and direct negative control paradigm. (D)